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Dapagliflozin Effects on Hypoglycemia

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ClinicalTrials.gov Identifier: NCT03704818
Recruitment Status : Active, not recruiting
First Posted : October 15, 2018
Last Update Posted : September 29, 2021
Sponsor:
Collaborator:
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
Jeremy Pettus, MD, University of California, San Diego

Tracking Information
First Submitted Date  ICMJE October 8, 2018
First Posted Date  ICMJE October 15, 2018
Last Update Posted Date September 29, 2021
Actual Study Start Date  ICMJE October 8, 2018
Actual Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 11, 2018)
  • Glucagon Response to Hypoglycemia [ Time Frame: 12 Weeks ]
    Participants will undergo a baseline hypoglycemic clamp during which glucagon will be measured. Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing glucagon.
  • Epinephrine Response to Hypoglycemia [ Time Frame: 12 Weeks ]
    Participants will undergo a baseline hypoglycemic clamp during which epinephrine will be measured. Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing epinephrine.
  • Norepinephrine Response to Hypoglycemia [ Time Frame: 12 Weeks ]
    Participants will undergo a baseline hypoglycemic clamp during which norepinephrine will be measured. Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing norepinephrine.
  • Cortisol Response to Hypoglycemia [ Time Frame: 12 Weeks ]
    Participants will undergo a baseline hypoglycemic clamp during which cortisol will be measured. Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing cortisol.
  • Growth Hormone Response to Hypoglycemia [ Time Frame: 12 Weeks ]
    Participants will undergo a baseline hypoglycemic clamp during which growth hormone will be measured. Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing growth hormone.
  • Hypoglycemia Awareness [ Time Frame: 12 Weeks ]
    Participants will undergo a baseline hypoglycemic clamp during which they will complete the Edinburgh Hypoglycemia Scale (EHS). Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing the EHS.
  • Trails Making B Performance Response to Hypoglycemia [ Time Frame: 12 Weeks ]
    Participants will undergo a baseline hypoglycemic clamp during which they will complete the cognitive test, Trails Making B. Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing Trails Making B.
  • Digit Symbol Substitution Performance Response to Hypoglycemia [ Time Frame: 12 Weeks ]
    Participants will undergo a baseline hypoglycemic clamp during which they will complete the cognitive test, Digit Symbol Substitution. Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing Digit Symbol Substitution.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dapagliflozin Effects on Hypoglycemia
Official Title  ICMJE Evaluating the Effect of Dapagliflozin, an SGLT-2 Inhibitor, on the Counterregulatory Response to Hypoglycemia in Individuals With Type 1 Diabetes
Brief Summary The purpose of this research study will be to test and evaluate if dapagliflozin has an effect on the amount of glucagon (a hormone produced by the pancreas and stomach that stimulates liver glucose production) produced by the body and if that change will improve recovery time from hypoglycemia (low blood sugar) in participants with Type 1 Diabetes.
Detailed Description The purpose of this research study will be to test and evaluate if dapagliflozin has an effect on the amount of glucagon (a hormone produced by the pancreas and stomach that stimulates liver glucose production) produced by the body and if that change will improve recovery time from hypoglycemia (low blood sugar) in participants with Type 1 Diabetes. The study is a blinded, placebo-controlled, crossover design, where participants will receive dapagliflozin during one treatment period and placebo during a separate treatment period with neither the study team nor participants knowing what they are receiving at any given time. Participants will have 9 clinic visits over the course of 14-16 weeks, with 3 of those visits being overnight stays. The overnight stays are intended to control blood sugars in a normal state throughout the night and then participants will complete a hypoglycemic challenge the following morning. The body's response to the hypoglycemic challenge will provide the information needed to determine if dapagliflozin had an effect on recovery time from hypoglycemia.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Type1 Diabetes Mellitus
Intervention  ICMJE
  • Drug: Dapagliflozin 5mg
    Dapagliflozin treatment taken daily for 4-weeks.
    Other Name: Farxiga
  • Drug: Placebo Oral Tablet
    Placebo treatment taken daily for 4-weeks.
Study Arms  ICMJE
  • Experimental: Dapagliflozin 5mg
    Intervention: Drug: Dapagliflozin 5mg
  • Experimental: Placebo
    Intervention: Drug: Placebo Oral Tablet
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: October 11, 2018)
22
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 30, 2021
Actual Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Signed and dated written informed consent by the date of Visit 1 in accordance with Good Clinical Practice (GCP) and local legislation
  2. Male or female patient receiving insulin for the treatment of documented diagnosis of T1DM for at least 1 year at the time of Visit 1
  3. Non-fasting C-peptide < 0.7 ng/mL at Visit 1
  4. HbA1c ≤ 10.0% at Visit 1
  5. Based on the Investigator's judgment patient must have a good understanding of his/her disease and how to manage it, and be willing and capable of performing the following study assessments (assessed at Visits 1):

    • patient-led management and adjustment of insulin therapy
    • reliable approach to insulin dose adjustment for meals, such as carbohydrate counting
    • reliable and regular home-based blood glucose monitoring
    • be able to perform ketone sample measurement when feeling ill and/or nauseated
    • implementation of an established "sick day" management regimen
  6. Age ≥ 18 and ≤ 70 years at Visit 1
  7. Body Mass Index (BMI) of 18.5 kg/m2 to 35.0 kg/m2 at Visit 1
  8. eGFR ≥ 60 mL/min/1.73m²
  9. Patients must be able and willing to perform study assessments

Exclusion Criteria:

  1. History of T2DM, maturity onset diabetes of the young (MODY), pancreatic surgery or chronic pancreatitis
  2. Pancreas, pancreatic islet cells or renal transplant recipient
  3. T1DM treatment with any other antihyperglycemic drug (e.g. metformin, alpha- glucosidase inhibitors, SGLT-2 inhibitors, pramlintide, inhaled insulin, pre-mixed insulins, etc.) within 30 days of run-in (visit 2)
  4. Occurrence of severe hypoglycemia involving coma and/or seizure that required hospitalization or hypoglycemia-related treatment by an emergency physician or paramedic within 3 months prior to Visit 1 or Visit 2
  5. Occurrence of DKA within 3 months prior to Visit 1 or Visit 2
  6. Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris), stroke or transient ischemic attack (TIA) within 3 months prior to Visit 1 or Visit 2
  7. Indication of liver disease, defined by serum levels of either alanine transaminase (ALT), aspartate transaminase (AST), or alkaline phosphatase above 3 x upper limit of normal (ULN) at Visit 1
  8. Current signs and symptoms of anemia accompanied by a hemoglobin laboratory value at or below 10.0 g/dL at screening.
  9. Eating disorders such as bulimia or anorexia nervosa
  10. Treatment with systemic corticosteroids within 30 days of run-in (visit 2), or planned initiation of such therapy at Visit 1 or Visit 2. Inhaled or topical use of corticosteroids (e.g. for asthma/chronic obstructive pulmonary disease) is acceptable.
  11. Medical history of cancer or treatment for cancer in the last five years prior to Visit 1. Resected basal cell carcinoma considered cured is exempted.
  12. Women who are pregnant, nursing, or who plan to become pregnant while in the trial
  13. Intake of an investigational drug in another trial within 30 days prior to Visit 1
  14. Patient not able to understand and comply with study requirements, based on Investigator's judgment
  15. Any other clinical condition that, based on Investigator's judgment, would jeopardize patient safety during trial participation or would affect the study outcome (e.g. immunocompromised patients who might be at higher risk of developing genital or mycotic infections, patients with chronic viral infections etc.)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03704818
Other Study ID Numbers  ICMJE UC-MEDJP-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Jeremy Pettus, MD, University of California, San Diego
Study Sponsor  ICMJE University of California, San Diego
Collaborators  ICMJE Juvenile Diabetes Research Foundation
Investigators  ICMJE Not Provided
PRS Account University of California, San Diego
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP